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Oral cancer genesis and progression: DNA near-diploid aneuploidization and endoreduplication by high resolution flow cytometry

Article type: Research Article

Authors: Donadini, Alessandra; | Maffei, Massimo; | Cavallero, Antonio | Pentenero, Monica | Malacarne, Davide | Di Nallo, Emanuela | Truini, Mauro | Navone, Roberto | Mereu, Paola | Scala, Marco | Santelli, Alida | Gandolfo, Sergio | Giaretti, Walter;

Affiliations: Department of Diagnostic Oncology, Biophysics and Cytometry Section, National Cancer Research Institute, Genoa, Italy | Department of Otolaryngology, San Martino Hospital, Genoa, Italy | Department of Clinical and Biological Sciences, Oral Medicine and Oral Oncology Section, University of Turin, Turin, Italy | Department of Diagnostic Oncology, Pathology Section, National Cancer Research Institute, Genoa, Italy | Department of Biomedical Sciences and Human Oncology, Pathology Section, University of Turin, Turin, Italy | Department of Surgical Oncology, Oral Surgery Section, National Cancer Research Institute, Genoa, Italy

Note: [] These authors contributed equally to the study.

Note: [] Corresponding author: Dr. Walter Giaretti, Laboratory of Biophysics and Cytometry, Department of Diagnostic Oncology, National Cancer Research Institute, Largo Rosanna Benzi, n. 10, 16132 Genoa, Italy. Tel.: +39 010 5737 461 (464); Fax: +39 010 5737 546; E-mail: [email protected].

Keywords: Oral field effect carcinogenesis, oral potentially malignant lesions, oral squamous cell carcinomas, DNA aneuploidy, flow cytometry

DOI: 10.3233/CLO-2010-0525

Journal: Analytical Cellular Pathology, vol. 32, no. 5-6, pp. 373-383, 2010

Published: 2010
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Abstract

Oral potentially malignant lesions (OPMLs) with dysplasia and aneuploidy are thought to have a high risk of progression into oral squamous cell carcinomas (OSCCs). Non-dysplastic “oral distant fields” (ODFs), characterized by clinically normal appearing mucosa sited at a distance from co-existing OPMLs, and non-dysplastic OPMLs may also represent an early pre-cancerous state. ODFs, OPMLs without and with dysplasia and OSCCs were investigated by high resolution DNA content flow cytometry (FCM). ODFs and OPMLs without dysplasia were DNA aneuploid respectively in 7/82 (8.5%) and 25/109 (23%) cases. “True normal oral mucosa” and human lymphocytes from healthy donors were DNA diploid in all cases and were used as sex specific DNA diploid controls. Dysplastic OPMLs and OSCCs were DNA aneuploid in 12/26 (46%) and 12/13 (92%) cases. The DNA aneuploid sublines were characterized by the DNA Index (DI≠1). Aneuploid sublines in ODFs and in non-dysplastic and dysplastic OPMLs were near-diploid (DI<1.4) respectively in all, 2/3 and 1/3 of the cases. DNA aneuploid OSCCs, instead, were characterized prevalently by multiple aneuploid sublines (67%), which were commonly (57%) high-aneuploid (DI≥1.4). DNA near-diploid aneuploid sublines in ODFs and OPMLs appear as early events of the oral carcinogenesis in agreement with the concept of field effect. Near-diploid aneuploidization is likely to reflect mechanisms of loss of symmetry in the chromosome mitotic division. High DNA aneuploid and multiple sublines in OPMLs with dysplasia and OSCCs suggest, instead, mechanisms of “endoreduplication” of diploid and near-diploid aneuploid cells and chromosomal loss. High resolution DNA FCM seems to enable the separation of subsequent progression steps of the oral carcinogenesis.

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